This is a competing continuation application for a NIDA Drug Abuse Research Training Program conducted at the Alcohol and Drug Abuse Research Center, McLean Hospital and Harvard Medical School. A multidisciplinary clinical and preclinical training program is offered to postdoctoral fellows who have been awarded an M.D., Ph.D., M.D.-Ph.D., or D.V.M. The faculty includes scientists trained in Pharmacology, Neurology, Internal Medicine, Neurobiology, Medicinal Chemistry, Psychiatry and Psychology with active research programs that involve brain imaging, neuroendocrinology, pharmacology, behavioral science, genetics, neuroscience and medicinal chemistry. The 12 member faculty has academic appointments as Assistant, Associate and full Professor or Lecturer at the Harvard Medical School. Trainees have an opportunity to participate in clinical research on drug abuse treatment, clinical laboratory evaluations of novel medications, the acute and chronic biomedical effects of abused drugs on neuroendocrine and immune function, and brain function using functional magnetic resonance imaging. Basic science fellows can receive training in medicinal chemistry, brain imaging techniques, drug self-administration and drug discrimination procedures, analysis of analgesic efficacy, and neuroendocrinology. Fellows can participate in studies of the pharmacological characterization of novel opioid and dopaminergic compounds, the evaluation of candidate treatment medications and analgesics, the effects of abused drugs on the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonadal axis, and the modulation of the endocrine and behavioral effects of drugs by the hormonal milieu. This Center has had a long-standing interest in the role of gender and neuroendocrine hormones in the effects of abused drugs. This research program is especially concerned with issues related to drug abuse problems in women. Trainees initially participate in one or more ongoing research projects with their mentors. Then trainees design an independent research project, compatible with the overall research goals of the program. The trainee's formal protocol is reviewed by mentors and by external scientific advisors. These trainee pilot projects are intended to form the basis for a research application, and the overall goal of the program is to train young scientists to conduct independent research on drug abuse. Trainees are taught about ethical issues that affect research and learn about IRB and IACUC procedures. Trainees take courses, participate in a journal club, attend lectures and scientific meetings and present research findings. Each trainee's program is individually tailored to meet his/her training objectives. Fifteen of our recent trainees have independent research grants and/or junior faculty positions, and two will serve as mentors for the proposed renewal of this training program. Research reports by trainees have been published in outstanding biomedical journals including the Journal of Pharmacology and Experimental Therapeutics, JAMA, Magnetic Resonance in Medicine, Journal of Nuclear Medicine, Neuropsychopharmacology, Nature Neuroscience, Biological Psychiatry and Psychopharmacology.